High Myopia and Its Associated Factors in JPHC-NEXT Eye Study: A Cross-Sectional Observational Study

The increasing prevalence of high myopia has been noted. We investigated the epidemiological characteristics and the related factors of high myopia in a Japanese adult population. Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) Eye Study was performed in Chikusei-city, a rural area in mid-east Japan, between 2013 and 2015. A cross-sectional observational analysis was conducted to investigate prevalence and related factors of high myopia. A total of 6101 participants aged ≥40 years without a history of ocular surgeries was included. High myopia was defined as a spherical equivalent refraction of ≤-6.00 diopters according to the American Academy of Ophthalmology. Potential high myopia-related factors included intraocular pressure (IOP), corneal structure, corneal endothelial cell density, age, height, body mass index, heart rate, blood pressure, biochemical profile, and current history of systemic and ocular disorders. The odds ratios of high myopia were estimated using the logistic regression models adjusted for the associated factors. The prevalence of high myopia was 3.8% in males and 5.9% in females with a significant difference. Age was inversely associated, IOP was positively associated, and none of other factors were associated with high myopia in both sexes. In conclusion, only age and IOP were associated with high myopia in this community-based sample

AC and AG Dinucleotide Repeats in the PAX6 P1 Promoter are Associated with High Myopia

Purpose: The PAX6 gene, located at the reported myopia locus MYP7 on chromosome 11p13, was postulated to be associated with myopia development. This study investigated the association of PAX6 with high myopia in 379 high myopia patients and 349 controls. Methods: High myopia patients had refractive errors of –6.00 diopters or greater and axial length longer than 26 mm. Control subjects had refractive errors less than –1.00 diopter and axial length shorter than 24 mm. The P1 promoter, all coding sequences, and adjacent splice-site regions of the PAX6 gene were screened in all study subjects by polymerase chain reaction and direct sequencing. PAX6 P1 promoter-luciferase constructs with variable AC and AG repeat lengths were prepared and transfected into human ARPE-19 cells prior to assaying for their transcriptional activities. Results: No sequence alterations in the coding or splicing regions showed an association with high myopia. Two dinucleotide repeats, (AC)m and (AG)n, in the P1 promoter region were found to be highly polymorphic and significantly associated with high myopia. Higher repeat numbers were observed in high myopia patients for both (AC)m (empirical p = 0.013) and (AG)n (empirical p = 0.012) dinucleotide polymorphisms, with a 1.327-fold increased risk associated with the (AG)n repeat (empirical p = 0.016; 95% confidence interval: 1.059–1.663). Luciferase-reporter analysis showed elevated transcription activity with increasing individual (AC)m and (AG)n and combined (AC)m(AG)n repeat lengths. Conclusions: Our results revealed an association between high myopia and AC and AG dinucleotide repeat lengths in the PAX6 P1 promoter, indicating the involvement of PAX6 in the pathogenesis of high myopia

Early diagnosis and research of high myopia with primary open angle glaucoma

People with high myopia are high risk populations to have primary open angle glaucoma. Clinically, we found that patients with primary open angle glaucoma and high myopia is closely related. So to understand the clinical features of high myopia with primary open angle glaucoma and the importance of early diagnosis, to avoiding missed diagnosis or lower misdiagnosed rate, can help to improve the vigilance and level of early diagnosis of the clinicians. In this paper, high myopia with clinical features of primary open angle glaucoma, and the research progress on the main points of early diagnosis were reviewed

IMI impact of myopia

The global burden of myopia is growing. Myopia affected nearly 30% of the world population in 2020 and this number is expected to rise to 50% by 2050. This review aims to analyze the impact of myopia on individuals and society; summarizing the evidence for recent research on the prevalence of myopia and high myopia, lifetime pathological manifestations of myopia, direct health expenditure, and indirect costs such as lost productivity and reduced quality of life (QOL). The principal trends are a rising prevalence of myopia and high myopia, with a disproportionately greater increase in the prevalence of high myopia. This forecasts a future increase in vision loss due to uncorrected myopia as well as high myopia-related complications such as myopic macular degeneration. QOL is affected for those with uncorrected myopia, high myopia, or complications of high myopia. Overall the current global cost estimates related to direct health expenditure and lost productivity are in the billions. Health expenditure is greater in adults, reflecting the added costs due to myopia-related complications. Unless the current trajectory for the rising prevalence of myopia and high myopia change, the costs will continue to grow. The past few decades have seen the emergence of several novel approaches to prevent and slow myopia. Further work is needed to understand the life-long impact of myopia on an individual and the cost-effectiveness of the various novel approaches in reducing the burden

Divergence insufficiency associated with high myopia

Hiromi Kohmoto, Kenji Inoue, Masato WakakuraInouye Eye Hospital, Chiyoda-ku, Tokyo, JapanPurpose: Divergence insufficiency is generally regarded as a neurological event. While high myopia is not a well-known cause of divergence insufficiency, we frequently encounter divergence insufficiency in high-myopia patients. Thus, the purpose of this study was to report detailed information on such cases and examine mechanisms that might potentially be responsible for this disorder.Methods: We investigated 20 cases of high myopia (>-6 D) with divergence insufficiency, 20 cases of high myopia without double vision, and 10 normal cases as controls. Using magnetic resonance imaging (MRI), a coronal image 6 mm anterior to the eyeball–optic nerve junction was measured and used to examine the extraocular muscle (EOM) path shift and angle of the eye. Higher angles in each patient were used for statistical comparison.Results: In high-myopia patients with divergence insufficiency, ocular axis measurements ranged from 24.8 to 31.0 (mean ± SD: 27.6 ± 1.6) mm. In high-myopia patients without double vision, the ocular axis length was 27.6 ± 1.3 mm. In normal cases, the ocular axis length was 23.5 ± 1.0 mm. The EOM angles in these patients ranged from 100 to 140 (112.9 ± 9.7) degrees, which was significantly higher (P < 0.05) than that seen in the high-myopia patients without double vision (average EOM angle, 99.2 ± 2.8 degrees) and normal cases (average EOM angle, 97.9 ± 3.8 degrees). However, orbital lengths in the patients were 41.0 to 48.9 (44.6 ± 2.3) mm, which also differed from the high-myopia patients without double vision (average orbital length, 49.9 ± 2.0 mm) significantly (P < 0.05). In normal cases, average orbital length was 45.5 ± 1.6 mm.Conclusion: In high-myopia patients with divergence insufficiency, nasal shift of the superior rectus and an inferior shift of the lateral rectus were observed, but the orbital lengths were normal. Divergence insufficiency may be caused mechanically by shifts of the EOM due to the presence of a long axis. Therefore, high myopia with a long axis can be considered to be a risk factor for the occurrence of divergence insufficiency.Keywords: divergence insufficiency, high myopia, MRI, extraocular muscl

Exome Sequencing Identifies ZNF644 Mutations in High Myopia

Myopia is the most common ocular disorder worldwide, and high myopia in particular is one of the leading causes of blindness. Genetic factors play a critical role in the development of myopia, especially high myopia. Recently, the exome sequencing approach has been successfully used for the disease gene identification of Mendelian disorders. Here we show a successful application of exome sequencing to identify a gene for an autosomal dominant disorder, and we have identified a gene potentially responsible for high myopia in a monogenic form. We captured exomes of two affected individuals from a Han Chinese family with high myopia and performed sequencing analysis by a second-generation sequencer with a mean coverage of 30× and sufficient depth to call variants at ∼97% of each targeted exome. The shared genetic variants of these two affected individuals in the family being studied were filtered against the 1000 Genomes Project and the dbSNP131 database. A mutation A672G in zinc finger protein 644 isoform 1 (ZNF644) was identified as being related to the phenotype of this family. After we performed sequencing analysis of the exons in the ZNF644 gene in 300 sporadic cases of high myopia, we identified an additional five mutations (I587V, R680G, C699Y, 3′UTR+12 C>G, and 3′UTR+592 G>A) in 11 different patients. All these mutations were absent in 600 normal controls. The ZNF644 gene was expressed in human retinal and retinal pigment epithelium (RPE). Given that ZNF644 is predicted to be a transcription factor that may regulate genes involved in eye development, mutation may cause the axial elongation of eyeball found in high myopia patients. Our results suggest that ZNF644 might be a causal gene for high myopia in a monogenic form

Why acute decreased vision in patients with high myopia is an emergency?

We report a case of 43 years old women who present myopic CNV (A) causing an acute vision loss. That has not been treated at time causing a chorioretinal atrophy as the angiography (B) and her Optical Coherence Tomography (OCT) (C) shows. High myopia is a major cause of legal blindness in many countries, especially in young people. Itis defined as a refraction of at least -6.00 diopters and/or an axial length upper than 25.5 mm. Excessive axial elongation of the globe in high myopia can cause mechanical stretching of the choroid and retinal layers, causing a degenerative changes. It is well known that individuals with high myopia have increased risks of retinal complications such as peripheral retinal degenerations, retinal detachment, choroidal neovascularisation (CNV) and macular haemorrhage. Among various lesions associated with high myopia, macular CNV is the most vision threatening complications.It develops in around 10% of eyes with high myopia. CNV is the creation of new blood vessels in the choroid layer of the eye. The disease can progress to chorioretinal atrophy (Fuchs spot).Patients may develop metamorphopsia, central scotoma and decreased visual acuity. Recently, the use of angiogenesis therapy with anti-vascular endothelial growth factor (VEGF) agents like intravitreal bevacizumab has demonstratedencouraging results and hadbecome the treatment of choice for myopic CNV

Myocilin polymorphisms and high myopia in subjects of European origin

Purpose: Three previous studies have tested for an association between high myopia and polymorphisms in the open angle glaucoma gene, myocilin (MYOC), all in subjects of Chinese ethnicity. In two of the studies, a significant association was found while in the third, there was no association. We sought to investigate the association between high myopia and polymorphisms in MYOC in subjects of European ethnicity. Methods: Subjects were recruited from two sites, Cardiff University in the UK and Duke University in the United States. The Cardiff University cohort was comprised of 164 families with high myopia (604 subjects) plus 112 unrelated, highly myopic cases and 114 emmetropic controls. The Duke University cohort was comprised of 87 families with high myopia (362 subjects) plus 59 unrelated, highly myopic cases. Subject DNA was genotyped with a panel of MYOC single nucleotide polymorphisms (SNPs) including those found previously associated with high myopia. The Cardiff cohort was also genotyped for two flanking microsatellite markers analyzed in prior studies. Association between high myopia and MYOC polymorphisms was assessed using the Unphased program. Results: Since there was no evidence of heterogeneity in genotype frequencies between families and singleton samples or between cohorts, both subject groups (families and unrelated subjects) from both recruitment sites were analyzed jointly for those SNPs genotyped in common. Two variants showed significant association before correction for multiple testing. These two variants were rs16864720 (p=0.043) and NGA17 (p=0.026). However, there was no significant association after Bonferroni correction. The estimated relative risk (RR) conferred by each of the MYOC variants was low (RR<1.5). Conclusions: Our results suggest that MYOC polymorphisms have a very low, or possibly negligible, influence on high myopia susceptibility in subjects of European ethnicity

The association of a single nucleotide polymorphism in the promoter region of the LAMA1 gene with susceptibility to Chinese high myopia

Purpose: High myopia is a severe hereditary ocular disease leading to blindness. LAMA1 (alpha subunit of laminin) is a promising candidate gene for high myopia present in the MYP2 (myopia 2) region. The purpose of this study was to determine if high myopia is associated with single nucleotide polymorphism (SNP) variants in LAMA1 in Chinese subjects. Methods: Ninety-seven Chinese subjects with high myopia and ethnically and sexually matched 103 normal controls were enrolled. Genomic DNA was prepared from peripheral blood. The 5 SNPs of LAMA1 were analyzed using PCR and SNaPshot. Allele frequencies were tested for Hardy-Weinberg disequilibrium. The genotype and allele frequencies were evaluated using the χ2 tests or the Fisher exact tests. Results: One of the 5 SNPs showed a significant difference between patients and control subjects (rs2089760: pgenotype=0.005, pallel=0.003). There were no statistically significant differences between patients and control subjects for the other four SNPs: rs566655, rs11664063, rs607230, and rs3810046. Conclusions: Our results indicate that the polymorphism of rs2089760, located in the promoter region of LAMA1, may be associated with high myopia in the Chinese population and should be investigated further. © 2011 Molecular Vision.link_to_subscribed_fulltex